Protein biomarkers in the serum hold great promise in non-invasive disease detection and management. Prostate cancer is the most frequently diagnosed non-cutaneous malignancy and the second leading cause of cancer related deaths among men in the United States. Currently available treatment modalities are usually ineffective in advanced stages and the disease must, therefore, be diagnosed early. At present, early diagnosis is based on DRE and PSA assay and is subsequently confirmed by biopsy. These tests, however, lack sensitivity and specificity. Although hormonal therapy initially is effective at blocking tumor growth, these therapies usually fail, leading to lethal androgen independent prostate cancer (AIPC). Despite several modifications of PSA test, its specificity as a diagnostic and/or prognostic biomarker remains compromised. The major goal of the proposed studies is to identify a panel of serum biomarkers that are more sensitive and specific that, either independently or in conjunction with PSA, will facilitate in early diagnosis and more importantly in the management of clinically relevant prostate cancer. During the first phase, we will monitor levels of t-PSA, IL-8, TNF-a, & sTNF-R1 in AIPC patients and compare them to controls. The main objective here is to identify serum biomarkers that will be more predictive of disease prognosis. We will study correlation between levels of these biomarkers and disease stage, treatment, patient response/survival etc. Preliminary studies suggest that TNF-a levels in AIPC patients are significantly higher as compared to controls. During the second phase, we will measure the levels of t-PSA, IL-8, TNF-a, and sTNF-R1 in (a) early stage prostate cancer (CaP) patients, (b) in BPH patients and in (c) healthy controls. We will evaluate if any one group has significantly altered levels of these biomarkers. The goal is to identify a serum biomarker(s) that can be specific in identifying early stage CaP and also differentiate between BPH and CaP. We have shown that serum levels of IL-8 and sTNF-R1 are significantly higher in CaP patients as compared to controls. We will study the correlation between serum levels of these biomarkers and conventional prognostic criteria including Gleason scores. New biomarkers that will have clinical impact and will facilitate to maximize the use of current therapies and to evaluate the future novel, potentially more effective therapies are needed. [unreadable] [unreadable]